Portal Hypertension in Nonalcoholic Fatty Liver Disease: Challenges and Paradigms

Abstract

Portal hypertension in cirrhosis is defined as an increase in the portal pressure gradient (PPG) between the portal and hepatic veins and is traditionally estimated by the hepatic venous pressure gradient (HVPG), which is the difference in pressure between the free-floating and wedged positions of a balloon catheter in the hepatic vein. By convention, HVPG≥10 mmHg indicates clinically significant portal hypertension, which is associated with adverse clinical outcomes. Nonalcoholic fatty liver disease (NAFLD) is a common disorder with a heterogeneous clinical course, which includes the development of portal hypertension. There is increasing evidence that portal hypertension in NAFLD deserves special considerations. First, elevated PPG often precedes fibrosis in NAFLD, suggesting a bidirectional relationship between these pathological processes. Second, HVPG underestimates PPG in NAFLD, suggesting that portal hypertension is more prevalent in this condition than currently believed. Third, cellular mechanoresponses generated early in the pathogenesis of NAFLD provide a mechanistic explanation for the pressure-fibrosis paradigm. Finally, a better understanding of liver mechanobiology in NAFLD may aid in the development of novel pharmaceutical targets for prevention and management of this disease.

The role of anoctamin 1 in liver disease

“…Interestingly, in vivo experiments yielded opposite results, with ANO1 expression significantly downregulated in the portal vein of rats with PHT 32 . Notably, elevated portal pressure is the main feature of PHT, 94,95 and these findings provide new ideas for the development of PHT. In addition, a recent study showed that in PVSMCs in a model of cirrhotic PHT, angiotensin II (ANGII) reduced vascular tone and contraction by downregulating the expression of ANO1, 96 but the underlying mechanism is unclear and requires further investigation.…”

Choice of antihyprtensive therapy at varios stages of metabolically associated lever disease

“…Прогрессирование МАСБП в ряде случаев осложняется развитием портальной гипертензии [37]. В этот период заболевания для контроля над уровнем артериального давления пациентов целесообразно использовать гипотензивные препараты, оказывающие влияние как на системную, так и портальную гипертензию.…”